Time of Hope for the Eventual Elimination of Meningococcal Strains A, C, Y, and W-135 in the United States

In this issue of American Family Physician, Dr. Kimmel expertly reviews meningococcal disease and meningococcal vaccines.1

Meningococcal disease is devastating, causing death in 10 to 14 percent of patients and serious complications in about another 11 to 19 percent despite the use of antibiotics.2 These complications include hearing loss, limb loss, and neurologic disability. One fourth of patients have serious or fatal complications.

Meningococcal disease is uncommon, with an incidence rate of 0.5 to 1.1 cases per 100,000 persons per year, and most cases are sporadic.2 The incidence rate is highest in preschool-age children; a smaller peak occurs in adolescents and young adults.

Until recently, the only vaccine available was a polysaccharide vaccine that has several limitations: it does not provide good immunity in young children, because they do not respond well to polysaccharide antigens; the duration of immunity is moderate; it does not provide an anamnestic response; and it does not lead to sustained reduction in nasopharyngeal carriage.

Recently, tetravalent meningococcal conjugate vaccine was licensed for persons 11 to 55 years of age. Because it is a conjugate vaccine, it has the potential for use in young children. (A supplemental license application has been filed with the U.S. Food and Drug Administration [FDA] for ages two to 10 years, but it is not yet approved for this age group.) The vaccine has a 73 to 97 percent immunogenicity based on a fourfold or greater rise in serum bactericidal activity, and 97 to 100 percent immunogenicity based on achieving a geometric mean titer of 128 or greater.2 As a conjugate vaccine, it may reduce nasopharyngeal carriage and produce some herd immunity once in widespread use in multiple age groups. Local injection site pain occurs in 54 to 59 percent of recipients, but severe pain occurs in only 0.2 to 0.3 percent. Some patients (16 to 17 percent) will develop local induration, but only 3 to 4 percent will develop induration of 1 inch or more.

The vaccine is recommended by the Advisory Committee on Immunization Practices (ACIP) for several groups: (1) persons 11 to 12 years of age, (2) those who need to catch up before entry into high school (about 15 years of age), (3) college freshman, (4) military recruits, and (5) other persons at high risk (e.g., certain international travelers to hyperendemic regions, exposed microbiologists, persons with asplenia or terminal complement deficiencies).2 Unfortunately, at $633,000 per case prevented and $5 million per death prevented, vaccination is not cost-effective for adolescents.3

As of October 2, 2005, five reports of a possible association between the newly licensed tetravalent meningococcal conjugate vaccine and Guillain-Barré syndrome have been filed with the Vaccine Adverse Event Reporting System (VAERS), which is operated by the Centers for Disease Control and Prevention (CDC) and the FDA. All five case reports occurred in adolescents 17 to 18 years of age. Each patient had onset of Guillain-Barré syndrome symptoms 14 to 31 days after vaccination. Of note, the five patients received their respective vaccines from four different lots. The CDC reports that the incidence of Guillain-Barré, based on the number of cases reported within six weeks of receiving the vaccine, is similar to what might have been expected to occur by chance alone, but notes that adverse events temporarily associated with vaccines should be reported to VAERS. As a result, the CDC supports ACIP’s recommendations but states that not vaccinating patients who are known to have previously had Guillain-Barré syndrome is prudent. Physicians should be aware of the recent case reports and expect further information from the CDC as the investigation progresses.4

Despite this potential cause for pause, what excites me about meningococcal conjugate vaccine is the potential to eliminate or greatly reduce meningococcal serotypes A, C, Y, and W-135 disease from the United States. The United Kingdom instituted monovalent serogroup C conjugate vaccine in November 1999. Subsequently, disease attack rates dropped in the vaccinated; carriage rates dropped; and then the incidence declined among unvaccinated persons, suggesting herd immunity.5 Widespread vaccination in a number of age groups will be needed for this to occur in the United States, including preschool-age children, for whom the vaccine currently is not licensed. Unfortunately, serotype B is not in the vaccine, so some meningococcal disease still will occur.

The Author

RICHARD K. ZIMMERMAN, M.D., M.P.H., is associate professor in the Department of Family Medicine and Clinical Epidemiology at the University of Pittsburgh School of Medicine, with a secondary appointment in the Department of Behavioral and Community Health Sciences. He was a past voting member of the Advisory Committee on Immunization Practices and the AAFP Commission on Clinical Policies and Research.

Address correspondence to Richard K. Zimmerman, M.D., M.P.H., Department of Family Medicine and Clinical Epidemiology, University of Pittsburgh School of Medicne, 3518 Fifth Ave., Pittsburgh, PA 15261 (e-mail: zimmer+@pitt.edu). Reprints are not available from the author.